The major goal of this research plan is to study the relationship between abnormal carbohydrate metabolism and the development of hypertriglyceridemia. During the next year we plan to focus our efforts in two general areas. Current results from our laboratory suggest that fructose-induced hypertriglyceridemia in normal rats is associated with an increase in plasma insulin levels. In addition, it appears that the hyperinsulinemia is accompanied by a loss of normal insulin sensitivity. During the next year we shall attempt to focus on the mechanism of the apparent fructose-induced loss of normal insulin sensitivity. In order to do this we will feed fructose to rats and measure various aspects of insulin action in both liver and muscle. Our second major area of interest in the next year will be to study the relationship between insulin binding and endogenous hypertriglyceridemia in man. More specifically, we will attempt to see if there is a correlation between loss of insulin receptors, the biological effect of insulin, and development of endogenous hypertriglyceridemia.